At homeostasis, vascular cells display a very low proliferative rate and a scant migratory activity. However, hyperplastic growth and locomotion of vascular cells are a hallmark of vascular remodeling during several pathophysiological conditions (e.g., neovascularization, arteriosclerosis and restenosis post-angioplasty). Thus, a better understanding of the molecular mechanisms that control vascular cell proliferation and migration should facilitate the development of novel therapies to treat cardiovascular disease. In this review, we will discuss recent studies implicating the cell cycle regulatory protein p27Kip1 as a key modulator of vascular cell growth and locomotion in vitro and during vascular remodeling in vivo.